Inflammasomes are immune complexes whose activation leads to the release of pro-inflammatory cytokines IL-18 and IL-1β. Type I IFNs play a role in fighting infection and stimulate the expression of IFN-stimulated genes (ISGs) involved in inflammation. Despite the importance of these cytokines in inflammation, the regulation of inflammasomes by type I IFNs remains poorly understood. Here, we analysed RNA-sequencing data from patients with monogenic interferonopathies and found an up-regulation of several inflammasome-related genes. To investigate the effect of type I IFN on the inflammasome, we treated human monocyte-derived macrophages with IFN-α and observed an increase inCASP1andGSDMDmRNA levels over time, whereasIL1BandNLRP3were not directly correlated to IFN-α exposure time. IFN-α treatment reduced the release of mature IL-1β and IL-18, but not caspase-1, in response to ATP-mediated NLRP3 inflammasome activation, suggesting regulation occurs at cytokine expression levels and not the inflammasome itself. However, more studies are required to investigate how regulation by IFN-α occurs and impacts NLRP3 and other inflammasomes at both transcriptional and post-translational levels.

Cytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-17), anti-inflammatory cytokines (IL-4 and IL-10), Brain-derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and fractalkine were unaffected in response to laser-induced OHT in both the OHT eye and its contralateral eye. Only IL-6 levels were significantly increased in the OHT eye one day after laser induction compared with the control group. These results differed from those observed in animals subjected to unilateral OHT and not treated with saffron, where changes in cytokine levels occurred in both eyes. Therefore, saffron extract regulates the production of proinflammatory cytokines, VEGF, and fractalkine induced by increasing intraocular pressure (IOP), protecting the retina from inflammation. These results indicate that saffron could be beneficial in glaucoma by helping to reduce the inflammatory process.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

Early life stress (ELS) is associated with an increased risk for neuropsychiatric disorders, and both neuroinflammation and mitochondrial dysfunction seem to be central to mental health. Herein, using an animal model of ELS, a single episode of maternal deprivation (MD, 24 h on pnd 9) extensively documented to elicit behavioural anomalies in male and female Wistar rats, we investigated its consequences in terms of neuroinflammation and mitochondrial dynamics in the prefrontal cortex (PFC) and the hippocampal formation (HCF). MD differentially affected the brain content of cytokines: MD induced a transient increase in pro-inflammatory cytokines (IL-1β and IL-6) in the PFC, as well as in the levels of the anti-inflammatory cytokine IL-10 in the HCF. MD also induced a significant decrease mitochondria citrate synthase activity, but MD did not exert significant changes in mitochondria Complex IV activity, revealing a generalized decrease in mitochondrial density without any change in mitochondrial respiration. In the present study, we demonstrate that MD induces neuroinflammatory processes in specific brain regions. Additional research is needed to better understand the temporal pattern of such changes, their impact on the developing brain, and their participation in the already well-known behavioural consequences of MD.

Aim: It is assumed that natremia remains low throughout the duration of chronic hyponatremia, inducing symptoms. We explore Recurrent Intermittent Hyponatremia (RIH) to establish whether a few hours of hyponatremia per day are enough to induce significant water retention. Methods: A rat model of RIH was developed and compared to control animals. Electrolyte balance and central nervous system (CNS) (water content and cellular changes) were studied at baseline and after a water overload equivalent to 10% of the animal’s body weight. Apparent diffusion coefficient (ADC) obtained through magnetic resonance was used to study changes in content and distribution of brain water. Immunohistochemistry techniques were used to study in the CNS astroglial cells through the glial fibrillary acidic-protein (GFAP) expression; as well as oligodendrocytes and the myelin sheath using the myelin basic protein (MBP) antibody. Blood and urine analysis were performed to assess water and electrolyte balance. Results: In RIH, mild hyponatremia was induced, but recovered after 24h; this situation was repeated for 7 consecutive days. A lower ADC value in the whole brain compared to control animals suggested an increase in total brain water in this situation. An increase in GFAP expression in the gray matter (GM) was observed, while MBP’s expression remained unchanged. The water overload on RIH induced hypotonic hyponatremia, progressively decreased ADC values in the whole brain (less pronounced than in controls), and increased GFAP and MBP’s expression in the white matter (similar increase found in controls). Conclusion: RIH is a novel animal model that suggests there can be significant water retention after only a few hours of hyponatremia a day provided this situation is repeated over time. Such water retention translates into a greater brain water accumulation and astroglial activation in the GM.